Bacteroides fragilis enterotoxin induces formation of autophagosomes in endothelial cells but interferes with fusion with lysosomes for complete autophagic flux through a mitogen-activated protein kinase-, AP-1-, and C/EBP homologous proteindependent pathway

Su Hyuk Ko, Jong Ik Jeon, Hyun Soo Myung, Young Jeon Kim, Jung Mogg Kim

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), plays an essential role in mucosal inflammation. Although autophagy contributes to the pathogenesis of diverse infectious diseases, little is known about autophagy in ETBF infection. This study was conducted to investigate the role of BFT in the autophagic process in endothelial cells (ECs). Stimulation of human umbilical vein ECs (HUVECs) with BFT increased light chain 3 protein II (LC3- II) conversion from LC3-I and protein expression of p62, Atg5, and Atg12. In addition, BFT-exposed ECs showed increased indices of autophagosomal fusion with lysosomes such as LC3-lysosome-associated protein 2 (LAMP2) colocalization and the percentage of red vesicles monitored by the expression of dual-tagged LC3B. BFT also upregulated expression of C/EBP homologous protein (CHOP), and inhibition of CHOP significantly increased indices of autophagosomal fusion with lysosomes. BFT activated an AP-1 transcription factor, in which suppression of AP-1 activity significantly downregulated CHOP and augmented autophagosomal fusion with lysosomes. Furthermore, suppression of Jun N-terminal protein kinase (JNK) mitogenactivated protein kinase (MAPK) significantly inhibited the AP-1 and CHOP signals, leading to an increase in autophagosomal fusion with lysosomes in BFT-stimulated ECs. These results suggest that BFT induced accumulation of autophagosomes in ECs, but activation of a signaling pathway involving JNK, AP-1, and CHOP may interfere with complete autophagy.

Original languageEnglish (US)
Article numbere00420-17
JournalInfection and immunity
Volume85
Issue number10
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • Autophagy
  • Bacteroides fragilis enterotoxin
  • Endothelial cells

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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